STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses
DNA vaccines elicit antibody, T helper cell responses and CD8+ T cell responses. Currently, little is known about the mechanism that DNA vaccines employ to induce adaptive immune responses. Prior studies have demonstrated that stimulator of interferon genes (STING) and conventional dendritic cells (...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.861710/full |
| _version_ | 1818061529902219264 |
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| author | Justin Theophilus Ulrich-Lewis Justin Theophilus Ulrich-Lewis Kevin E. Draves Kevin E. Draves Kelsey Roe Kelsey Roe Megan A. O’Connor Edward A. Clark Edward A. Clark Deborah Heydenburg Fuller |
| author_facet | Justin Theophilus Ulrich-Lewis Justin Theophilus Ulrich-Lewis Kevin E. Draves Kevin E. Draves Kelsey Roe Kelsey Roe Megan A. O’Connor Edward A. Clark Edward A. Clark Deborah Heydenburg Fuller |
| author_sort | Justin Theophilus Ulrich-Lewis |
| collection | DOAJ |
| description | DNA vaccines elicit antibody, T helper cell responses and CD8+ T cell responses. Currently, little is known about the mechanism that DNA vaccines employ to induce adaptive immune responses. Prior studies have demonstrated that stimulator of interferon genes (STING) and conventional dendritic cells (cDCs) play critical roles in DNA vaccine induced antibody and T cell responses. STING activation by double stranded (dsDNA) sensing proteins initiate the production of type I interferon (IFN),but the DC-intrinsic effect of STING signaling is still unclear. Here, we investigated the role of STING within cDCs on DNA vaccine induction of antibody and T cell responses. STING knockout (STING-/-) and conditional knockout mice that lack STING in cDCs (cDC STING cKO), were immunized intramuscularly with a DNA vaccine that expressed influenza A nucleoprotein (pNP). Both STING-/- and cDC STING cKO mice had significantly lower type I T helper (Th1) type antibody (anti-NP IgG2C) responses and lower frequencies of Th1 associated T cells (NP-specific IFN-γ+CD4+ T cells) post-immunization than wild type (WT) and cDC STING littermate control mice. In contrast, all mice had similar Th2-type NP-specific (IgG1) antibody titers. STING-/- mice developed significantly lower polyfunctional CD8+ T cells than WT, cDC STING cKO and cDC STING littermate control mice. These findings suggest that STING within cDCs mediates DNA vaccine induction of type I T helper responses including IFN-γ+CD4+ T cells, and Th1-type IgG2C antibody responses. The induction of CD8+ effector cell responses also require STING, but not within cDCs. These findings are the first to show that STING is required within cDCs to mediate DNA vaccine induced Th1 immune responses and provide new insight into the mechanism whereby DNA vaccines induce Th1 responses. |
| first_indexed | 2024-12-10T13:49:46Z |
| format | Article |
| id | doaj.art-7fa6674b841f48979e62717e444a10e7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T13:49:46Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7fa6674b841f48979e62717e444a10e72022-12-22T01:46:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.861710861710STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody ResponsesJustin Theophilus Ulrich-Lewis0Justin Theophilus Ulrich-Lewis1Kevin E. Draves2Kevin E. Draves3Kelsey Roe4Kelsey Roe5Megan A. O’Connor6Edward A. Clark7Edward A. Clark8Deborah Heydenburg Fuller9Department of Microbiology, University of Washington, Seattle, WA, United StatesDepartment of Immunology, University of Washington, Seattle, WA, United StatesDepartment of Microbiology, University of Washington, Seattle, WA, United StatesDepartment of Immunology, University of Washington, Seattle, WA, United StatesDepartment of Immunology, University of Washington, Seattle, WA, United StatesSeattle Children's Hospital Center for Immunity and Immunotherapies Children’s Hospital, Seattle, WA, United StatesDepartment of Microbiology, University of Washington, Seattle, WA, United StatesDepartment of Microbiology, University of Washington, Seattle, WA, United StatesDepartment of Immunology, University of Washington, Seattle, WA, United StatesDepartment of Microbiology, University of Washington, Seattle, WA, United StatesDNA vaccines elicit antibody, T helper cell responses and CD8+ T cell responses. Currently, little is known about the mechanism that DNA vaccines employ to induce adaptive immune responses. Prior studies have demonstrated that stimulator of interferon genes (STING) and conventional dendritic cells (cDCs) play critical roles in DNA vaccine induced antibody and T cell responses. STING activation by double stranded (dsDNA) sensing proteins initiate the production of type I interferon (IFN),but the DC-intrinsic effect of STING signaling is still unclear. Here, we investigated the role of STING within cDCs on DNA vaccine induction of antibody and T cell responses. STING knockout (STING-/-) and conditional knockout mice that lack STING in cDCs (cDC STING cKO), were immunized intramuscularly with a DNA vaccine that expressed influenza A nucleoprotein (pNP). Both STING-/- and cDC STING cKO mice had significantly lower type I T helper (Th1) type antibody (anti-NP IgG2C) responses and lower frequencies of Th1 associated T cells (NP-specific IFN-γ+CD4+ T cells) post-immunization than wild type (WT) and cDC STING littermate control mice. In contrast, all mice had similar Th2-type NP-specific (IgG1) antibody titers. STING-/- mice developed significantly lower polyfunctional CD8+ T cells than WT, cDC STING cKO and cDC STING littermate control mice. These findings suggest that STING within cDCs mediates DNA vaccine induction of type I T helper responses including IFN-γ+CD4+ T cells, and Th1-type IgG2C antibody responses. The induction of CD8+ effector cell responses also require STING, but not within cDCs. These findings are the first to show that STING is required within cDCs to mediate DNA vaccine induced Th1 immune responses and provide new insight into the mechanism whereby DNA vaccines induce Th1 responses.https://www.frontiersin.org/articles/10.3389/fimmu.2022.861710/fullDNA vaccineSTINGdendritic cellstype I interferoncGAS |
| spellingShingle | Justin Theophilus Ulrich-Lewis Justin Theophilus Ulrich-Lewis Kevin E. Draves Kevin E. Draves Kelsey Roe Kelsey Roe Megan A. O’Connor Edward A. Clark Edward A. Clark Deborah Heydenburg Fuller STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses Frontiers in Immunology DNA vaccine STING dendritic cells type I interferon cGAS |
| title | STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses |
| title_full | STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses |
| title_fullStr | STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses |
| title_full_unstemmed | STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses |
| title_short | STING Is Required in Conventional Dendritic Cells for DNA Vaccine Induction of Type I T Helper Cell- Dependent Antibody Responses |
| title_sort | sting is required in conventional dendritic cells for dna vaccine induction of type i t helper cell dependent antibody responses |
| topic | DNA vaccine STING dendritic cells type I interferon cGAS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.861710/full |
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